Previous chapters in this series by Warren appeared in 1955 (310) and 1966 (311). Since then an authoritative book by Bull, Culvenor, and Dick, on the chemistry and pharmacology of pyrrolizidine alkaloids has been published (60). Comprehensive reviews on the alkaloids (312), their chemotaxonomic significance (77), and general pyrrolizidine chemistry (243) are available. A series of Annual Reports including pyrrolizidine alkaloids was introduced in 1971 (245). The present review follows the format of previous articles in this series and covers the literature up to early 1981.

The pyrrolizidine alkaloids.

The development of high-quality herbage is an important aspect of animal husbandry. Inoculating beneficial fungi onto inferior grass is a feasible strategy for producing new varieties of high-quality herbage. Epichloe bromicola is a candidate fungus that is isolated from Elymus tangutorum. A total of 17 metabolites, 1-17, were obtained from E. bromicola, and their biological activities were assayed. Metabolite 1 exhibited antifungal activities against Alternaria alternata, Fusarium avenaceum, Bipolaris sorokiniana, and Curvularia lunata. EC50 values ranged from 0.7 to 5.3 μM, which were better than the positive control, chlorothalonil. Metabolite 8 displayed obvious phytotoxic effects toward Lolium perenne and Poa crymophila seedlings, and it was as active as glyphosate. None of these isolated metabolites displayed cytotoxicity against Madin-Darby bovine kidney cells. The IC50 values were greater than 100 μM, and the metabolites increased the growth of the cells at a concentration of 12.5 μM. The bioassay indicated that E. bromicola may be a beneficial fungus for producing new varieties of herbage with various resistances. Additionally, metabolite 7, 3-(2'-(4″-hydroxyphenyl)acetoxy)-2S-methylpropanoic acid, is a new natural product, and its stereochemistry was determined by means of optical rotation computation and chemical reactions.

Antifungal, Phytotoxic, and Cytotoxic Activities of Metabolites from Epichloë bromicola, a Fungus Obtained from Elymus tangutorum Grass.

Total synthesis of optically active monocrotaline, a carcinogenic pyrrolizidine alkaloid possessing an eleven-membered retronecine dilactone

In order to assign the absolute configuration of C-15 in natural 16-hydroxyferruginol, (5S,10S,15R)- (1a) and (5S,10S,15S)-8,11,13-abietatriene-12,16-diol (1b) have been synthesized. Optical resolution of 2-(2-methoxyphenyl)propanoic acid, prepared from methyl (2-methoxyphenyl)acetate, with cinchonidine afforded (R)- and (S)-enantiomers, which were converted into [(R)-4-methoxy-3-(2-methoxy-1-methylethyl)benzyl]triphenylphosphonium chloride (3a) and its (S)-isomer (3b) respectively. The Wittig reaction of (R)-(−)-α-cyclocitral with 3a, followed by partial catalytic hydrogenation and intramolecular cyclization gave (5S,10S, 15S)-12,16-dimethoxy-8,11,13-abietatriene (16a) together with its (5S,10R,15R)-isomer. Similarly, 3b was also converted into (5S,10S,15S)-12,16-dimethoxy-8,11,13-abietatriene (16b) and its (5S,10R,15S)-isomer. Demethylation of 16a gave 1a which was identical with natural 16-hydroxyferruginol. The dimethoxy compound 16b was also demethylated to give 1b.

The total synthesis of (15R)- and (15S)-16-hydroxyferruginol.

Total synthesis of optically active monocrotaline, a carcinogenic pyrrolizidine alkaloid having an 11-membered dilactone

All stereoisomers (3a, b–6a, b) of monocrotalic acid have been synthesized. Methylation of (±)-cis-2,3,4-trimethyl-2-pentenedioic acid with diazomethane followed by cis-hydroxylation with potassium permanganate afforded two epimeric γ-lactone esters in a ratio of ca. 1:5. These esters were then hydrolyzed with dilute hydrochloric acid to the corresponding acids, (±)-3 and racemic monocrotalic acid (4). Optical resolution of (±)-3 with brucine afforded 3a (2R,3R,4S) and 3b (2S,3S,4R). The racemic monocrotalic acid was also resolved by means of brucine to give natural monocrotalic acid (4a: 2R,3R,4R) and its enantiomer (4b: 2S,3S,4S). Subsequently, (±)-trans-2,3,4-trimethyl-2-pentenedioic acid was resolved with cinchonidine to give 8a and 8b, whose stereochemistry was assigned respectively as S- and R-configuration by correlation to the known (R)-(−)-2-phenylpropanoic acid. Methylation of 8a followed by cis-hydroxylation and hydrolyses afforded γ-lactone acids, 5a (2R,3S,4S) and 6b (2S,3R,4S). Similarly, th...

Makoto Takahashi

Papers

Pyrrolizidine Alkaloids. The Synthesis and Absolute Configuration of All Stereoisomers of Monocrotalic Acid

Pyrrolizidine alkaloids. the synthesis and absolute configuration of all stereoisomers of monocrotalic acid